This proposal is to request funding for the purchase of a Mark I Model 68 Cesium-137 gamma irradiator. The instrument will be located adjacent to an exclusion barrier animal facility. This placement will fulfill an essential need for the ability to irradiate mice and other research animals under pathogen-free conditions and then continuously house them for longitudinal studies. Several instrument users require this capacity to prepare recipient animals for bone marrow transplantation in order to study host immune mechanisms, as well as the role of bone marrow stem cells in tumorigenesis. In addition, the irradiation of genetically modified mice is a requirement of several investigators studying DNA damage response pathways and mechanisms for the maintenance of genomic stability. The irradiator will also be used extensively for the irradiation of cultured cells and other biological samples, and its highly accessible, central location in close proximity to user laboratories will greatly facilitate such uses. These include the irradiation of embryonic stem cells in order to induce chromosomal deletions, human tumor cells for the development of therapeutic strategies based on radiation-induced apoptosis, and mammalian tissue culture cells for studies of DNA damage responses. Several users, including the Cornell Core Transgenic Mouse Facility, will employ the instrument to prepare irradiated feeder cells for use in the generation and maintenance of embryonic stem cell cultures. Finally, the irradiator will be used by additional investigators for studies of meiotic recombination in maize and as a means to modulate parasite infectivity for analysis of host-pathogen interactions. In sum, the gamma irradiator will fulfill critical needs for a broad and diverse user group initially consisting of seventeen investigators and will significantly enhance NIH-funded research at Cornell University. This proposal requests funding for instrumentation essential to the completion of a variety of NIH-funded research projects. These proposed studies will yield important insights into immune system function, cancer biology, and vertebrate development, and will improve our understanding of how certain human diseases arise and how they can be treated effectively. [unreadable] [unreadable] [unreadable]